【作者】 相成；

【导师】 田建明； 陆建平； 杨继金； 左长京；

【作者基本信息】 第二军医大学 ， 影像医学与核医学， 2006， 博士

【摘要】 通过建立兔VX₂肝移植瘤模型探讨了不同时相VX₂肿瘤的影像学及病理特征,为进一步评价功能影像学在肝癌消融疗效预测提供合适的实验对象;通过评价兔VX₂肝移植瘤血流动力学参数与MVD、VEGF表达的相关性,探讨血流动力学参数对酒精消融治疗疗效预测的可能性及早期移植瘤血流动力学参数变化的特点;探讨1.5T双梯度磁共振对兔VX₂肝移植瘤进行弥散功能成像的可行性观察兔VX₂肝移植瘤模型的MR扩散加权成像（DWI）表现,并与肿瘤细胞密度等病理学变化进行对照,分析肝移植瘤DWI表现的病理学基础及DWI产生的ADC图在确定兔VX₂肝移植瘤肝内浸润范围中的价值。 第一部分:兔VX₂2肝移植瘤模型的建立及影像学评价。目的:建立一种适合医学影像学实验研究的稳定的兔VX₂肝移植瘤模型,通过CT、MRI、US及CT灌注功能成像观察兔VX₂肝癌生长、转移和血液供应情况,分析不同时相VX₂肿瘤的影像学及病理特征,为进一步评价功能影像学在肝癌消融前后提供合适的实验对象。材料和方法:新西兰大白兔30只,采用开腹直视下肿瘤组织块直接种植法建立兔VX₂肝癌模型。于种植后第7天、14天、21天、28天、35天行兔肝螺旋CT平扫和三期增强扫描,种植后第14天、21天另加行同层动态扫描。观察VX₂肿瘤的CT显示率,肿瘤的直径和体积变化,计算肿瘤生长率,有无远处转移及肿瘤的自然生存情况。获取肿瘤标本,常规HE染色,观察瘤组织病理特征。分析兔VX₂肝移植瘤的CT特征,分析兴趣区时间—密度曲线（T-DC）走势,并计算强化峰值（PV）和峰值时间（PT）。结果:肿瘤于种植后第7天,SCT显示率低,种植14天后瘤灶检出率为100%。瘤灶直径和体积于种植后14天、21天增长缓慢,种植后28天、35天增长迅速,肿瘤呈指数性生长,种植后21天瘤灶内出现坏死,种植后28天出现肝转移。CT平扫27例（90%）肿瘤表现为低密度灶,增强扫描动脉期瘤周显著环状强化,其中24例（80%）肿瘤可见供瘤动脉,门脉期和平衡期瘤周强化环密度减低,瘤边缘密度稍增高,有呈向心性强化的趋势,但不能完全充填病灶。瘤灶的TDC走势呈缓慢上升型,PT较正常肝实质出现早。组织病理学显示肿瘤在肝脏中呈浸润性生长,其边缘可见丰富的血管(包括静脉和毛细更多还原

【Abstract】 To evaluate the predictive value of the hepatic caner ablation therapeutic effect by function imaging and to analyze its imaging features and pathology feature with spiral computed tomography in different phase by the rabbit VX₂ hepatic tumor model. To evaluate correlation of the rabbit VX₂ hepatic tumor model haemodynamics parameter and MVD, VEGF expressed and to investigate the predictive value of precutaneous ethanol injection’s therapeutic effect and the ealy stage of VX₂ hepatic tumor’s haemodynamics parameter. To investigate the possibility and the accuracy of MR diffusion （DWI） derived ADC map in estimating extent of the rabbit VX₂ hepatic tumor in the liver using the new 1.5T and double grade-field scanner. The rabbit VX₂ hepatic tumor was evaluated by diffusion-weighted MRI and its DWI manifestations were compared with histopathologic changes such as cell density and tumor necrosis to analysis the pathologic changes of DWI.The first part: Establishment and imaging evaluation of rabbit VX₂ hepatic tumor model. Objective: To evaluate the feasibility of the rabbit VX₂ hepatic tumor model for imaging study, and to analyze its imaging features with spiral computed tomography （SCT）,et al. Materials and methods: A tumor was implanted into the liver of each of the 30 New Zealand white rabbits using a midline laparotomy. Hepatic tumors were created by injecting fragments of VX₂ tumor into the left lobe of the liver. Plain CT scan and contrast-enhanced CT scan were performed at the 7^th, 14^th, 21^th, 28^th and 35^th days after implantation respectively, and the dynamic contrast-enhanced CT were performed at a single level centered over the lesions at the 14^th and the 21^th days respectively. The observations were included: （1） The number of the lesions detected on CT;（2） The size of the lesions;and its metastases to other sites. （The growth rate of tumors was also calculated）;（3） The histopathological features of tumors;（4） The spiral CT features of tumors;（5） Peak value （PV）, peak time （PT） and the time—density curves（D-TC）of aorta, liver and tumor. Results: The success rate of transplanting tumor was 100%. Three lesions were detected by CT at the 7^th day after implantation. The diameter and volume grewslowly at the 14 th and the 21 * day after implantation, but grew quickly at the 28th and the 35th day after implantation. The tumor grew as exponential curve. Metastases were found at the 28th day after implantation. Histopathological examination showed the tumor grew in the Liver tissue and infiltrated into surrounding liver, and it had the similar hypodensity solitary lesion in unenhanced CT except 2 （10%） lesions to be homogeneous density during the 14th and the 21th day. In arterial phase, significant peripheral enhancement were observed, the dilated nutrition alarteries stretching straight to the margins in IS （75%） lesions, while the main bodies of tumors remained hypodensity. In portal phase and equilibrium phase, concentrically enhancement of tumors were detected. The density of tumors became heterogeneous on plain. CT scan at the 21 stday after implantation. PV of aorta, liver and tumor was 316.3⁴86.3HU,55.3⁷7.3HU, 26.5 111. 8HU respectively. PT of the tumors is earlier than that of the surrounding liver tissues. Conclusions: 1 .Metastatic rabbit VX2 liver tumor model is stableand easy to be established. Its growth cycle and success rate of transplanting are satisfactory. It is also a suitable model for imaging study. 2. The characteristics of the blood supply, the histobiological and pathophy-Biological features are similar to that of the hepatic cell carcinoma. 3.The position, number and the characteristic of growth and metastases can be detected by spiral CT at the 14th day after implantation. The blood supply of the tumor can be delineated by contrast enhanced CT and single lever dynamic SCT effectively and accurately. But the sensitivity of the SCT is lower within 7 days after the implantation. 4. SCT provides a method to evaluate the characteristic and the therapeutic effect of metastatic rabbitVX2 liver tumor model.The second part: Correlation study between haemodynamics parameter and MVD? VEGF predictive value of percutaneous ethanol injection （PEI） herapeutic effect. Objective: To evaluate correlation of the rabbit VX2 hepatic tumor modelhaemodynamics parameter and MVTK VEGF expressed and to investigate the predictive value of precutaneous ethanol injection’s therapeutic effect and the ealy stage of VX2 hepatic tumor’s haemodynamics parameter. Methods: A tumor was implanted into the liver of each of the 64 New Zealand white rabbits to built experiment animal models. After lw performing CT prefusion scan,then the next week before executing PEI injected in the tumor do the same work and in this time to operate percutaneous puncture for pathological examination to obtain the expressed level of tumor immunohistochemister staining VEGF> MVD.In the third and fifth week performing enhancement CT scanning respectively and calculating the viable tumor tissue correspondence burden. Perfusion parameters including blood flow （BF） , blood volume （BV） ,mean transit time （MTT） were calculated . The correlation analysis was analyzed between perfusion parameters and VEGF-. MVD ■, the third , fifth week tumor load respectively.To seek correlation factor then distinguish tumor by perfusion parameters and analysis the impact therapeutic effect for PEI. Results: BF has a positive correlation with VEGF and the fifth tumor load. Coefficient of correlation are0.81 and 0.84 respectively.BV has a positive correlation with MVD and a negative correlation. Coefficient of correlation are 0.77 and —0.79.Higher BV group manifestates lower tumor load in the third week and higher BF group after PEI in the fifth week manifestates higher tumor load. Conclusion: Perfusion haemodynamics parameter （BF> BV） can reflect the express lever of VEGF, MVD and has some extent to react VX2 hepatic tumor molecular biology distinction. It also has some extent precognition value of PEI therapeutic effect.The third part: Pilot studies of MR diffusion imaging in rabbit VX2 hepatic tumor model Objective :To investigate the possibility and the accuracy of MR diffusion （DWI） derived ADC map in estimating extent of the rabbit VX2 hepatic tumor in the liver using the new 1.5T and double grade-field scanner.The rabbit VX2 hepatic tumor was evaluated by diffusion-weighted MRI and its DWI manifestations were compared with histopathologic changes such as cell density and tumor necrosisto analysis the pathologic changes of DWI. Methods:After 14-21 days implantation of the rabbit VX2 hepatic tumor cell, 8tumor-bearing rabbits were examined with contrast-enhanced MRI and DWI and its manifestations of contrast-enhanced MRI and DWI were compared with pathologic changes. The distance of the tumor extent on the ADC map was compared with that measured on TiWI and T2WI. Results:Signals of edema,necrotic tissue, viable tumor, normal liver were characterized as iso-,hypo- orsignificantly hypointense on ADC map respectively. The VX2 hepatic tumor extent demonstrated on the ADC map was highly correlated with that demonstrated on TiWI （correlation coefficient 0.994, <0.01）,and with that demonstrated on T2WI （correlation coefficient 0.991, P<0.01）;Of the 8 cases of VX2 hepatic tumor , 7 cases presented with annular enhancement on the contrast-enhanced Tl-weighted image. The intensities of central part of those VX2 hepatic tumor were elevated greatly compared with the surrounding area of tumor on apparent diffusion coefficient maps. The ADC of central part and surrounding area were[（106.5±11.9）xl0"5 ],[（78.2±9.2）*10 " 5 ]mm 2/s respectively, there were significant differences between the two areas（t=8.26> PO.01）. In the pathologic specimen, massive necrosis originating from the central part of tumors can be detected and tumor cell density in central region decreased obviously. The cell densities of central part and surrounding area were（13±8）% , （40±5）% , significant difference existed between the two areas（t=6.55, P<0.01）. Conclusion ADC maps derived from the SSEPI-DWI provide a different contrast between viable tumor, peritumoral edema and tumor necrosis, ADC map are accurate in determining intramedullary extent of VX2 liver tumor;The present results indicate that water ADC can be used as measures of cell density and necrotic fraction of tumor to different necrosis from viable tissue. The differences of signal intensities on DWI can reflect microscopic changes of rabbit VX2 liver tumor.更多还原